期刊
JOURNAL OF BIOMEDICAL SCIENCE
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1423-0127-17-88
关键词
-
资金
- American Cancer Society
- National Cancer Institute [P50 CA098252, 1 RO1 CA114425-01, 1 P20 CA144801]
- [RO1 CA114425-01]
Background: Effective vaccination against human papillomavirus (HPV) represents an opportunity to control cervical cancer. Peptide-based vaccines targeting HPV E6 and/or E7 antigens while safe, will most likely require additional strategies to enhance the vaccine potency. Methods: We tested the HPV-16 E7 peptide-based vaccine in combination with a strategy to enhance CD4+ T help using a Pan HLA-DR epitope (PADRE) peptide and a strategy to enhance dendritic cell activation using the toll-like receptor 3 ligand, poly(I:C). Results: We observed that mice vaccinated with E7 peptide-based vaccine in combination with PADRE peptide and poly(I:C) generated better E7-specific CD8(+) T cell immune responses as well as significantly improved therapeutic anti-tumor effects against TC-1 tumors compared to E7 peptide-based vaccine with either PADRE peptide or poly(I:C) alone. Furthermore, we found that intratumoral vaccination with the E7 peptide in conjunction with PADRE peptide and poly(I:C) generates a significantly higher frequency of E7-specific CD8(+) T cells as well as better survival compared to subcutaneous vaccination with the same regimen in treated mice. Conclusions: The combination of PADRE peptide and poly(I:C) with antigenic peptide is capable of generating potent antigen-specific CD8+ T cell immune responses and antitumor effects in vaccinated mice. Our study has significant clinical implications for peptide-based vaccination.
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